Monovalent cation:proton antiporter-3

The Monovalent Cation (K⁺ or Na⁺):Proton Antiporter-3 (CPA3) Family (TC# 2.A.63) is a member of the Na⁺ transporting Mrp superfamily. The CPA3 family consists of bacterial multicomponent K⁺:H⁺ and Na⁺:H⁺antiporters. The best characterized systems are the PhaABCDEFG system of Sinorhizobium meliloti (TC# 2.A.63.1.1) that functions in pH adaptation and as a K⁺ efflux system, and the MnhABCDEFG system of Staphylococcus aureus (TC# 2.A.63.1.3) that functions as a Na⁺ efflux Na⁺:H⁺ antiporter.

A homologous, but only partially sequenced, system was earlier reported to catalyze Na⁺:H⁺ antiport in an alkalophilic Bacillus strain. PhaA and PhaD are respectively homologous to the ND5 and ND4 subunits of the H⁺-pumping NADH:ubiquinone oxidoreductase (TC #3.D.1). Homologous protein subunits from E. coli NADH:quinone oxidoreductase can functionally replace MrpA and MrpD in Bacillus subtilis.

Homologues of PhaA, B, C and D and Nha1, 2, 3 and 4 of an alkalophilic Bacillus strain are the Yuf(Mrp)T, U, V and D genes of Bacillus subtilis. In this system, YufT is believed to be responsible for Na⁺:H⁺ antiporter activity, but it does not have activity in the absence of other constituents of the operon.

The seven Pha proteins are of the following sizes (in #aas) and exhibit the following putative numbers of transmembrane α-helical spanners (TMSs):

All are predicted to be integral membrane proteins.

Corresponding values for the S. aureus Mnh system are:

In view of the complexity of the system, large variation in subunit structure, and the homology with NDH family protein constituents, a complicated energy coupling mechanism, possibly involving a redox reaction, cannot be ruled out.

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